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Fibroblast activation protein

Rong-Hua Yang, Shao-Hai Qi, Shu-Bin Ruan, Ze-Peng Lin, Yan Lin, Feng-Gang Zhang, Xiao-Dong Chen, Ju-Lin Xie
Epidermal growth factor (EGF)-like family members mediate a wide range of biological activities including cell proliferation and migration. Increasing evidence indicated that EGF plays an important role in the process of wound healing by stimulating fibroblast motility. The aim of this study was to see whether EGF-like domain 7 (EGFL7)-overexpressing epidermal stem cells (EGFL7-ESCs) would promote fibroblast proliferation and migration. We found that mRNA and protein levels of EGFL7 expression were significantly increased in EGFL7-ESCs...
October 20, 2016: Molecular and Cellular Biochemistry
Yukio Ozaki, Shogo Tamura, Katsue Suzuki-Inoue
Platelets play a key role in the pathophysiological processes of hemostasis and thrombus formation. However, platelet functions beyond thrombosis and hemostasis have been increasingly identified in recent years. A large body of evidence now exists which suggests that platelets also play a key role in inflammation, immunity, malignancy, and furthermore in organ development and regeneration, such as the liver. We have recently identified CLEC-2 on the platelet membrane, which induces intracellular activation signals upon interaction of a snake venom, rhodocytin...
2016: Thrombosis Journal
Mariya Markova, Olga Pivovarova, Silke Hornemann, Stephanie Sucher, Turid Frahnow, Katrin Wegner, Jürgen Machann, Klaus Jürgen Petzke, Johannes Hierholzer, Ralf Lichtinghagen, Christian Herder, Maren Carstensen-Kirberg, Michael Roden, Natalia Rudovich, Susanne Klaus, Ralph Thomann, Rosemarie Schneeweiss, Sascha Rohn, Andreas F H Pfeiffer
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat but may induce insulin resistance. We investigated the effects of diets high in animal protein vs plant protein, which differ in levels of methionine and BCAA, in subjects with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue...
October 17, 2016: Gastroenterology
J Y Dong, F Song, Y K Liu, X Q Wang
Objective: To simulate the environmental factors during the process of formation and evolution of hypertrophic scar, so as to explore the effects of moderate and severe hypoxia and low concentration of serum protein on the function of human hypertrophic scar fibroblasts (HSFs). Methods: Human HSFs were routinely cultured. Cells of the 3rd to the 6th passage were divided into 10.0% oxygen+ 10.0% fetal calf serum (FCS), 5.0% oxygen+ 5.0% FCS, and 0.5% oxygen+ 0.5% FCS groups according to the random number table...
October 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Qi Cao, Zheng-Dao Mao, Yu-Jia Shi, Yi Chen, Yun Sun, Qian Zhang, Lei Song, Li-Ping Peng
OBJECTIVE: To investigate the effects of microRNA-7 (miR-7) on the proliferation, migration and invasion of non-small cell lung cancer NSCLC) cells by targeting FAK through ERK/MAPK signaling pathway. METHODS: NSCLC tissues and adjacent normal tissues were obtained from 160 NSCLC patients after operation. NSCLC cell lines (A549, H1299 and H1355) and a normal human fetal lung fibroblast cell line (MRC-5) were obtained. NSCLC cells were assigned into miR-7 inhibitors, miR-7 mimics, blank, miR-7 mimics control, miR-7 inhibitors control, FAK siRNA and miR-7 inhibitors + FAK siRNA groups...
October 15, 2016: Oncotarget
Emily C Lumley, Acadia R Osborn, Jessica E Scott, Amanda G Scholl, Vicki Mercado, Young T McMahan, Zachary G Coffman, Jay L Brewster
The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR). In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress. Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm). Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM)...
October 20, 2016: Cell Stress & Chaperones
Ahmad Alodaib, Nara Sobreira, Wendy A Gold, Lisa G Riley, Nicole J Van Bergen, Meredith J Wilson, Bruce Bennetts, David R Thorburn, Corinne Boehm, John Christodoulou
Recent advances in next-generation sequencing strategies have led to the discovery of many novel disease genes. We describe here a non-consanguineous family with two affected boys presenting with early onset of severe axonal neuropathy, optic atrophy, intellectual disability, auditory neuropathy and chronic respiratory and gut disturbances. Whole-exome sequencing (WES) was performed on all family members and we identified compound heterozygous variants (c.[760C>A];[1528G>C];p.[(Gln254Lys);(Ala510Pro)] in the polyribonucleotide nucleotidyltransferase 1 (PNPT1) gene in both affected individuals...
October 19, 2016: European Journal of Human Genetics: EJHG
Kevin K Kim, Thomas H Sisson, Jeffrey C Horowitz
Lung fibrosis results from the cumulative effect of dysfunctional wound repair involving multiple cell types, including fibroblasts, epithelial cells and macrophages responding to an array of soluble and matrix mediated stimuli. Recent studies have shown that a tyrosine kinase inhibitor that targets FGF, VEGF and PDGF receptors can slow the rate of decline in pulmonary function in patients with idiopathic pulmonary fibrosis. However, each of these growth factor families is comprised of multiple ligands and receptors with pleiotropic activities on different cell types such that their broad inhibition might have both pro-fibrotic and anti-fibrotic effects, limiting the potential therapeutic efficacy...
October 19, 2016: Journal of Pathology
Yosuke Nakazawa, Mikako Oka, Megumi Funakoshi-Tago, Hiroomi Tamura, Makoto Takehana
PURPOSE: Although aquaporin 0 (AQP0) is a member of the AQP family, it has limited water permeability compared with other members. AQP0 may also have cell adhesion-related functions, but the evidence is still limited. Here, we studied the relationship of AQP0 to cell adhesion and determined the region required for cell adhesion. METHODS: L-cell fibroblasts stably expressing AQP0 or AQP1 (L-AQP0 or L-AQP1) were established. One group of cells was stained with CellTracker Red and cultured into a confluent monolayer, whereas the other group was loaded with CellTracker Blue and seeded over the monolayer...
October 18, 2016: Current Eye Research
Caojian Zuo
OBJECTIVE: Cardiac fibroblasts play a vital role in the progression of fibrotic cardiac remodeling in hypertensive and failing heart. Osteoglycin (OGN) is implicated as a key regulator of left ventricular mass. However, its precise molecular role in cardiac fibrosis remains unknown. This study aims to investigate the impact of OGN in hypertensive cardiac remodeling. DESIGN AND METHOD: OGN deficient mice and its wildtype (WT) littermates were subjected to either angiotensin II (Ang II) infusion or pressure overload induced by transverse aortic constriction (TAC)...
September 2016: Journal of Hypertension
Che Wei Liao, Chi Sheng Hung, Chia Hung Chou, Yen Tin Lin, Xue Ming Wu, Yi Yao Chang, Ying Hsien Chen, Vin Cent Wu, Yi Lwun Ho, Kwan Dun Wu, Yen Hung Lin
OBJECTIVE: Aldosterone induces myocardial fibrosis. The tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis and diastolic dysfunction, but the effect of aldosterone on TIMP-1 expression remains unclear. We tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. DESIGN AND METHOD: In the human study, we prospectively enrolled 54 patients with primary aldosteronism. Plasma TIMP-1 and echocardiographic parameters were measured...
September 2016: Journal of Hypertension
Joon-Ii Jun, Lester F Lau
The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that CCN2 can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, CCN2 induces fibroblast senescence through integrin α6β1-mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16(INK4a)...
October 18, 2016: Journal of Cell Communication and Signaling
Ling C Huang, Mercedes Salvador-Silva, Ronika S Leang
OBJECTIVES: To demonstrate correlations among in vitro assays used for assessing cytotoxicity of contact lens multipurpose solution (MPS) and propose the use of multiple assays as a part of preclinical evaluation for MPS biocompatibility assessment. METHODS: The effect of four different MPSs on cell cytotoxicity, metabolic activity, and membrane integrity was performed by evaluating toxicity, expression of tight junction protein zonula occludens-1, and transepithelial electrical resistance in human corneal epithelial cells and Chinese hamster fibroblasts cells...
October 3, 2016: Eye & Contact Lens
Estelle R Simo-Cheyou, George Vardatsikos, Ashok K Srivastava
We have previously demonstrated that the non-receptor protein tyrosine kinase (NR-PTK) c-Src is an upstream regulator of endothelin-1 (ET-1) and angiotensin II-induced activation of protein kinase B (PKB) signaling in vascular smooth muscle cells (VSMCs). We have also demonstrated that ET-1 potently induces the expression of the early growth response protein-1 (Egr-1), a zinc finger transcription factor that is overexpressed in models of vascular diseases, such as atherosclerosis. However, the involvement of c-Src in ET-1‑induced Egr-1 expression has not yet been investigated and its role in mitogen-activated protein kinase (MAPK) signaling remains controversial...
October 6, 2016: International Journal of Molecular Medicine
Ling Nie, Jing-Hong Zhao, Jiang Wang, Rong Song, Shan-Jun Zhu
Cardiac fibroblasts (CFs) play a key role in cardiac fibrosis by regulating the balance between extracellular matrix synthesis and breakdown. Although phosphatase and tensin homologue on chromosome 10 (PTEN) has been found to play an important role in cardiovascular disease, it is not clear whether PTEN is involved in functional regulation of CFs. In the present study, PTEN was overexpressed in neonatal rat CFs via recombinant adenovirus-mediated gene transfer. The effects of PTEN overexpression on cell-cycle progression and angiotensin II- (Ang II-) mediated regulation of collagen metabolism, synthesis of matrix metalloproteinases, and Akt/P27 signaling were investigated...
2016: BioMed Research International
Wei-Jun Wu, Wan-Wan Jia, Xin-Hua Liu, Li-Long Pan, Qiu-Yan Zhang, Di Yang, Xiao-Yan Shen, Liang Liu, Yi Zhun Zhu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H2S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1β-induced human rheumatoid fibroblast-like synoviocytes MH7A...
October 6, 2016: Redox Biology
Patricie Burda, Terttu Suormala, Dorothea Heuberger, Alexandra Schäfer, Brian Fowler, D Sean Froese, Matthias R Baumgartner
5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NADPH-dependent reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using FAD as the cofactor. Severe MTHFR deficiency is the most common inborn error of folate metabolism, resulting in hyperhomocysteinemia and homocystinuria. Approximately 70 missense mutations have been described that cause severe MTHFR deficiency, however, in most cases their mechanism of dysfunction remains unclear. Few studies have investigated mutational specific defects; most of these assessing only activity levels from a handful of mutations using heterologous expression...
October 14, 2016: Journal of Inherited Metabolic Disease
Mark Hanudel, Harald Jüppner, Isidro B Salusky
In chronic kidney disease, systemic inflammation is common and associated with mortality. The present study demonstrates that fibroblast growth factor 23 (FGF23) contributes to uremic inflammation by increasing hepatic expression and secretion of inflammatory cytokines. FGF23 binds to hepatic FGFR4, inducing calcineurin/nuclear factor of activated T-cell signaling, resulting in increased expression of interleukin 6 and C-reactive protein. The proinflammatory effects of FGF23 are inhibited by an isoform-specific FGFR4 blocking antibody and by cyclosporine, a calcineurin inhibitor...
November 2016: Kidney International
Sarah L Cuddihy, Sarah Drake, D Tim Harwood, Andrew I Selwood, Paul S McNabb, Mark B Hampton
Portimine is a recently discovered member of a class of marine micro-algal toxins called cyclic imines. In dramatic contrast to related compounds in this toxin class, portimine has very low acute toxicity to mice but is highly cytotoxic to cultured cells. In this study we show that portimine kills human Jurkat T-lymphoma cells and mouse embryonic fibroblasts (MEFs), with LC50 values of 6 and 2.5 nM respectively. Treated cells displayed rapid caspase activation and phosphatidylserine exposure, indicative of apoptotic cell death...
October 13, 2016: Apoptosis: An International Journal on Programmed Cell Death
Akio Morinobu, Shino Tanaka, Keisuke Nishimura, Soshi Takahashi, Goichi Kageyama, Yasushi Miura, Masahiro Kurosaka, Jun Saegusa, Shunichi Kumagai
In rheumatoid arthritis (RA), synovial fibroblasts (RA-SFs) accumulate in affected joints, where they play roles in inflammation and joint destruction. RA-SFs exhibit tumor-like proliferation and are resistant to apoptosis. Although RA-SF activation is well described, negative regulators of RA-SF activation are unknown. We previously reported that histone deacetylase (HDAC) inhibitors facilitate apoptosis in RA-SFs. Here we found that RA-SFs treated with the HDAC inhibitor Trichostatin A (TSA) exhibited an upregulation of the immediate early response gene X-1 (IEX-1)...
2016: PloS One
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